Lower extremity deep venous thrombosis (DVT) is uncommon in the pediatric population, but it can be associated with severe symptoms and potential long-term morbidity secondary to post-thrombotic syndrome. Inferior vena cava (IVC) atresia can predispose a patient to the development of extremity DVT. There is no clear consensus on optimal management of extensive extremity DVT in pediatric patients, especially in patients with IVC anomalies. We report a case of iliofemoral DVT in a 9-year-old boy with IVC atresia and presumed protein S deficiency that was treated successfully using pharmacomechanical thrombectomy and catheter-directed thrombolysis. He was maintained on long-term anticoagulation and remained symptom free at 6 months’ follow-up.